This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Background: In the context of the CIBC, simulation is defined as the prediction of the behavior of cells, tissues, and organs under simplifying assumptions over known anatomical domains in response to pre-determined boundary or initial conditions. The overall goal of the CIBC, according to this definition, is to provide biomedical scientists with access to comprehensive and sophisticated software tools with which to define the assumptions, the domains, and the initial or boundary conditions and, then, to carry out simulations using advanced and robust numerical and computation algorithms. Rationale: A natural synergy exists between simulation and the other faces of scientific computing that remains a core element of the goals and progress of the CIBC. Although computer based simulation has a relatively modern history, the basic elements of simulation are as old as mathematics. Predicting the trajectory of a cannonball or the pathways of the planets both make use of the two essential elements of simulation: mathematical equations that describe behavior and a means to solve those equations under realistic conditions. The need to solve equations complex enough to predict the behavior of physical, chemical, or biological systems has further linked the progress in simulation to advances in numerical mathematics and computing and, hence, to the dramatic improvements in computer hardware and software. Questions: To be useful for estimation, simulation formulations should be mathematically invertible and lead to unique answers. In some cases, however, unique inversion may be theoretically possible but not numerically stable if the resulting problem is physically ill- posed and the resulting numerical simulation ill-conditioned. A goal throughout this TRD will be to formulate simulation approaches that not only solve the initial problem posed as a simulation, but formulate them, wherever possible, in a way that permits an effective associated estimation formulation. Design &Methods: Parallel to other TRDs, the specific methods of this proposal focus on three broad objectives. The first objective is to provide a set of software tools for constructing and executing simulations related mostly, but not exclusively, to bioelectric fields in the body. The second is to make these software tools available to scientists and engineers in a structure that is flexible, portable, and extensible enough to allow them to use existing tools and develop new ones based on their own expertise and novel ideas. The third objective is driven by the need of biomedical computational researchers for access to documented data sets for validation and efficient software for verification and sensitivity analysis.